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Updated: Jun 5, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor

Published on: September 13, 2018

Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein

Bin Zhao1, Li Li, Qing Lu

  • 1Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA.

Genes & Development
|January 6, 2011
PubMed

Insights

Angiomotin (AMOT) proteins regulate the Hippo pathway by inhibiting YAP and TAZ, crucial for organ size. AMOT knockdown activates YAP/TAZ, disrupting cell contact inhibition, suggesting a tumor-suppressive role.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The Yes-associated protein (YAP) is a key regulator of organ size, promoting cell proliferation and inhibiting apoptosis.
  • The Hippo tumor suppressor pathway inhibits YAP activity through phosphorylation, leading to cytoplasmic retention and degradation.
  • Angiomotin (AMOT) family proteins are involved in various cellular processes, including cell adhesion and polarity.

Purpose of the Study:

  • To investigate a novel mechanism of YAP regulation by AMOT family proteins.
  • To elucidate the role of AMOT in the Hippo pathway and its connection to cell contact inhibition.
  • To determine if AMOT proteins possess tumor-suppressive functions.

Main Methods:

  • Knockdown of AMOT family protein AMOTL2 in Madin-Darby canine kidney (MDCK) cells.
  • Assessment of YAP localization, phosphorylation, and target gene expression.
  • Evaluation of cell contact inhibition in AMOTL2 knockdown cells, analyzing YAP and TAZ dependency.

Main Results:

  • AMOTL2 knockdown in MDCK cells led to YAP activation, characterized by decreased tight junction localization, reduced phosphorylation, nuclear accumulation, and induced target gene expression.
  • The YAP paralog, TAZ, was similarly regulated by AMOT.
  • AMOTL2 knockdown resulted in a loss of cell contact inhibition, dependent on YAP and TAZ functions.

Conclusions:

  • AMOT family proteins inhibit YAP and TAZ through AMOT-mediated tight junction localization, representing a novel regulatory mechanism within the Hippo pathway.
  • AMOT proteins may function as tumor suppressors by maintaining cell contact inhibition.
  • This study establishes a link between the Hippo pathway and cell contact inhibition via AMOT proteins.

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